Experiments designed to define further the metabolic regulation of hyaluronate turnover and its role in control of normal and abnormal muscle and connective tissue development and remodelling are detailed in this research proposal. Initial studies to be done on chick embryo fibroblast cultures will focus on the metabolic control of hyaluronate turnover. Specific emphasis will be placed on the characterization of hyaluronidase, its mode of action on hyaluronte substrate, and its role in the regulation hyaluronate levels. Compositional and functional similarities of this enzyme to lysosomal exoglycosidases will be sought. Based on these studies, the relationship of hyaluronate turnover to and the effect of perturbations of hyaluronate levels on specific aspects of cell behavior will be examined in skeletal, cardiac, and smooth muscle cell cultures, as well as in cultures of human fibroblasts. These studies have direct bearing on specific heritable disorders of connective tissue and on atherosclerosis, in which hyaluronate turnover may be aberrant.